This proposal attempts to test the relevance of covalent binding of chemical carcinogens to regulatory proteins in carcinogenesis. The lactose repressor serves as a model for a protein binding to DNA with sequence specificity. The effect of covalent linkage of carcinogen to the repressor on the repressor-DNA binding constant will be studied. Aromatic amino acids are speculated to be involved in sequence specific binding to DNA and covalent adducts of purine N-oxide carcinogen to tryptophan and tyrosine have been characterized in this laboratory. Other chemical carcinogens will be tested for their ability to covalently bind to aromatic amino acids. Products of the covalent linkage of carcinogens to the repressor will be characterized. Such a study involving the small proteins, ribonuclease and lysozyme is in progress.